An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial.

Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l.

Positive and negative parenting in conduct disorder with high versus low levels of callous-unemotional traits.

Less is known about the relationship between conduct disorder (CD), callous-unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9-18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD.

Incidence, characteristics, and survival following cardiopulmonary resuscitation in the quaternary neonatal intensive care unit.

Background: The contemporary characteristics and outcomes of cardiopulmonary resuscitation (CPR) in the neonatal intensive care unit (NICU) are poorly described. The objectives of this study were to determine the incidence, interventions, and outcomes of CPR in a quaternary referral NICU.

Methods: Retrospective observational study of infants who received chest compressions for resuscitation in the Children's Hospital of Philadelphia NICU between April 1, 2011 and June 30, 2015.

Economic Evaluation in Stratified Medicine: Methodological Issues and Challenges.

Background: Stratified Medicine (SM) is becoming a practical reality with the targeting of medicines by using a biomarker or genetic-based diagnostic to identify the eligible patient sub-population. Like any healthcare intervention, SM interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. Methodological standards and guidelines exist for economic evaluations in clinical pharmacology and are an important component for health technology assessments (HTAs) in many countries.

High gain hybrid graphene-organic semiconductor phototransistors.

Hybrid phototransistors of graphene and the organic semiconductor poly(3-hexylthiophene-2,5-diyl) (P3HT) are presented. Two types of phototransistors are demonstrated with a charge carrier transit time that differs by more than 6 orders of magnitude. High transit time devices are fabricated using a photoresist-free recipe to create large-area graphene transistors made out of graphene grown by chemical vapor deposition.

Predictors of functional disability in rheumatoid arthritis: results from a 13-year prospective study.

Purpose: To explore the role of distress and social support as modifiers of functional disability in rheumatoid arthritis (RA). We hypothesized that: (a) higher inflammatory activity, more joint tenderness and more pain lead to more disability, and (b) that more distress and less social support lead to more disability and accelerate the disablement process by moderating the effects of inflammatory activity, joint tenderness and pain.

Methods: The study is a Dutch extension of the European Research on Incapacitating Diseases and Social Support (EURIDISS) which started with 292 patients.

Long-term health-related quality of life after lung transplantation: different predictors for different dimensions.

Background: Lung transplantation has proven to be an effective treatment option for patients with end-stage lung disease with profound effects on both survival and health-related quality of life (HRQL). Generally, studies have reported improved HRQL after lung transplantation. When assessing HRQL, physical, psychologic or social dimensions are usually included.

Blood damage, platelet and clotting activation during application of radiofrequency or cryoablation catheters: a comparative in vitro study.

During catheter ablation of cardiac tissue, the insulting stimulus may damage and activate the blood. Specifically activation of platelets and the clotting system is a potential risk by their formation of thrombi. In this study the effect of two different techniques, a radiofrequency and a cryo-application procedure, on the activation of platelets and clotting in an in vitro blood circulation model was investigated.

Role of phosphoinositide metabolism in human bronchial smooth muscle contraction and in functional antagonism by beta-adrenoceptor agonists.

The aim of the present investigation was to study in human bronchial smooth muscle (1) the relationship between methacholine and histamine-induced inositol phosphate (IP) production and contraction, (2) the influence of increasing concentrations of methacholine and histamine on the relaxation (pD2 and Emax) by isoproterenol (functional antagonism), and (3) the relation between IP production by methacholine and histamine and the changes of pD2 and Emax values of isoproterenol-induced relaxation. Methacholine and histamine were full agonists in contracting human bronchial smooth muscle, with pD2 values of 6.01 +/- 0.

Defective biliary secretion of bile acid 3-O-glucuronides in rats with hereditary conjugated hyperbilirubinemia.

Biliary secretion of bile acid glucuronides was studied in control rats and in rats with a congenital defect in hepatobiliary transport of organic anions (GY rats). In control animals, hepatobiliary transport of [3H]lithocholic acid 3-O-glucuronide and [3H]cholic acid 3-O-glucuronide was efficient (greater than 95% in 1 h) and comparable to that of [14C]taurocholic acid. Secretion of both glucuronides was impaired in GY rats (24% and 71% at 1 h), whereas that of taurocholate was similar to control values.

In vivo identification and quantitative evaluation of carrier-mediated transport of lactate at the cellular level in the striatum of conscious, freely moving rats.

Intracerebral dialysis has allowed the continuous, on-line measurement of lactate in the extracellular fluid (ECF) of conscious, freely moving rats. The rapid time response of the technique allows the direct determination of the time course of changes in lactate in ECF following externally imposed stimuli. The time course of lactate appearance in ECF was found to be considerably slower than that observed in tissue following electroconvulsive shock or during ischemia following cardiac arrest.